Based on theoretical considerations an explanation for the temperature dependence of the thermal expansion and the bulk modulus is proposed. A new equation state is also derived. Additionally a physical explanation for the latent heat of fusion is presented. These theoretical predictions are tested against experiments on highly symmetrical monoatomic structures. The volume is not an independent variable and must be broken down into its fundamental components when the relationships to the pressure and temperature are defined. Using zero pressure and temperature reference frame, the initial parameters, volume at zero pressure and temperature[VJ, bulk modulus at zero temperature[Ko], and volume coefficient of thermal expansion at zero pressure [a J are defined. The new derived EoS is tested against the experiments on perovskite and epsilon iron. The Root-mean-square-deviations (RMSD) of the residuals of the molar volume, pressure, and temperature are in the range of the uncertainty of the experiments. Separating the experiments into 200 K ranges, the new EoS was compared to the most widely used finite strain, interatomic potential, and empirical isothermal EoSs such as the Burch-Murnaghan, the Vinet, and the Roy-Roy respectively. Correlation coefficients, RMSD’s of the residuals, and Akaike Information Criteria were used for evaluating the fitting. Based on these fitting parameters, the new p-V-T EoS is superior in every temperature range relative to the investigated conventional isothermal EoS. The new EoS for epsilon iron reproduces the preliminary-reference earth-model (PREM) densities at 6100-7400 K indicating that the presence of light elements might not be necessary to explain the Earth’s inner core densities. It is suggested that the latent heat of fusion supplies the energy required for overcoming on the viscous drag resistance of the atoms. The calculated energies for melts formed from highly symmetrical packing arrangements correlate very well with experimentally determined latent heat values. The optical investigation of carbonado-diamond is also part of the dissertation. The collected first complete infrared FTIR absorption spectra for carbonado-diamond confirm the interstellar origin for the most enigmatic diamonds known as carbonado.

abstract: Research indicates that adults are not acquiring enough physical activity. Increasing the use of stairs is an accessible way to weave high intensity physical activity into the daily routine. The purpose of this study is to test the effect of four environmental changes on ascending stair use in a mixed population of college students, faulty, and staff on a southwest college campus. The study design included a 10-week time series design with alternating baseline and intervention phases, including a directional cue represented by footprints on the ground, a positive prompt, a deterrent prompt and a combination phase. Data was collected with both an in-person tally and a video recording device. The study included 6,140 observations and coded variables included stair use, sex, number of bags carried, temperature, and volume. Rater reliability ranged from .81 to 1.0. Multivariate logistic regression was used to perform the statistic analysis. Stair use increased significantly from Washout 1 and the positive prompting phase with a 7% absolute increase and an odds ratio of 1.35 (95% CI 1.080-1.696). Stair use during the footprint phase, deterrent phase and combination phase did not increase significantly compared to the previous baseline or washout phases. Day of the week (Monday=reference, Tuesday CI=1.626, 95% CI 1.298-2.011, Wednesday OR=0.457, 95% CI 0.248-0.841, Thursday OR=1.434, 95% CI 1.164-1.766), sex (OR=1.376, 95% CI 1.173-1.613) and volume (OR=1.007, 95% CI 1.005-1.008) were significantly correlated to stair use. Women used the stairs more than men and higher volume situations were related to increased stair use. Temperature and baggage number were not related to stair use. The results of this study indicate that positive prompting with an environmental message theme is an effective method to increase stair use in a university setting. / Dissertation/Thesis / Masters Thesis Exercise and Wellness 2015

<p> The pediatric mental health burden in the United States (US) is substantial, with more than 4 million children meeting diagnostic criteria for a mental health disorder. As of 2014, this number represented 20% of US children and adolescents. In 2010, mental health disorders are estimated to cost children and their families $247 billion dollars annually and severely impact quality of life for children and their families. From 2007 to 2010, inpatient admissions for mental health disorders in pediatric patients increased 24% and mood disorder admissions in pediatric patients increased 80% from 1997&ndash;2010. An estimated $11.6 billion was spent on pediatric mental health hospitalizations from 2006 through 2011, with public sources such as Medicaid and Medicare responsible for approximately 50% of the payments, leaving 50% to private payers. This economic and clinical concern has led pediatric medical associations and health quality agencies to increase support and funding for pediatric mental health research and treatment. </p><p> Medication therapy is a common intervention in mental health treatment and atypical antipsychotics are increasing in utilization, often becoming first-line therapy. Despite available data describing the need to treat pediatric mental health conditions, the available evidence for clinical effectiveness and economic impact of atypical antipsychotics (AAPs) has many shortfalls. Most available research is derived from patients utilizing publicly-funded medical care, such as Medicaid or Medicare resources, with little data available about patients with privately-funded care. To help address this gap in the literature, we used a large, privately-insured, US population for our analysis. We examined if the increased trend in AAP utilization from previous research is also present in this pediatric population. Considering the payer perspective, we evaluated the cost of AAP medication therapy based on most recent utilization. </p><p> Available studies lack information about the direct costs of pediatric mental health treatment and efficacy of psychiatric medications in the pediatric population. Most efficacy studies are based on clinical trials necessary for pediatric indication approval from regulatory agencies such as the Food and Drug Administration (FDA). Many of the AAP medications do not have pediatric clinical trial evidence available and are frequently utilized without pediatric indications. The available data suggests that off-label prescribing is not an uncommon practice in the pediatric patient population. </p><p> Approximately half of atypical antipsychotics do not have pediatric indications but are increasingly used, particularly in treating behavior disorders, due to such factors as improved patient compliance and improved side effect profiles. Limited formal studies examining atypical antipsychotic use compared to other agents in the class have been conducted. Studies with direct comparisons have yet to be conducted in the pediatric population with mental health disorders. </p><p> The manuscripts that comprise this dissertation aim to provide new insights into available trend and utilization patterns of atypical antipsychotic medication use in children. This research characterized the prevalence of atypical antipsychotic use in pediatric patient with mental health conditions in a large, privately insured US population, evaluating the diagnoses associated with treatment and estimate the cost of AAP medication therapy in this population. This research determined if the trends observed in publicly-insured children persist in the privately-insured, pediatric patient. The analysis evaluated annual trends in prevalent use of atypical antipsychotic medication over 6-year period in this pediatric population and evaluated the appropriate use of AAPs for mental health diagnoses. Lastly, an evaluation determined if specific antipsychotic therapy delayed time to readmission among privately-insured children following a psychiatric hospital admission. The results of this dissertation will provide new insights regarding the trends and direct medication costs of atypical antipsychotic agents when utilized in pediatric patients with mental health disorders. </p><p> <u>Manuscript 1:</u> This analysis focused on characterizing the most recent (2015) AAP use in the pediatric population, using a large, US population of privately- insured children. The study evaluated if the prevalence data observed among publicly insured children persists. Characterization of the prescribing trends for atypical antipsychotics and the medication costs of the use in this population were examined. Patterns of use across demographics and associated mental health diagnoses were characterized by the class of medication. This study focused on the prevalent use of AAPs in pediatric patients, evaluated the mental health diagnoses associated with AAPs and the direct cost burden of medication therapy associated with this use of AAP in the pediatric population to the private payer. </p><p> <u>Manuscript 2:</u> This research evaluated the trends in the prescribing of atypical antipsychotic medications from 2010 through 2015 in this privately-insured pediatric population. The trends of AAP use in the pediatric population over six years were examined. The associated mental health diagnoses corresponding with AAP prescribing were described to examine the off-label diagnoses treatment prevalence in this population. (Abstract shortened by ProQuest.) </p><p>

Learning at any-time, at anywhere, using any mobile computing platform learning (which we refer to as “education in your palm”) empowers informal and formal education. It supports the continued creation of knowledge outside a classroom, after-school programs, community-based organizations, museums, libraries, and shopping malls with under-resourced settings. In doing so, it fosters the continued creation of a cumulative body of knowledge in informal and formal education. Anytime, anywhere, using any device computing platform learning means that students are not required to attend traditional classroom settings in order to learn. Instead, students will be able to access and share learning resources from any mobile computing platform, such as smart phones, tablets using highly dynamic mobile and wireless ad-hoc networks. There has been little research on how to facilitate the integrated use of the service description, discovery and integration resources available in mobile and wireless ad-hoc networks including description schemas and mobile learning objects, and in particular as it relates to the consistency, availability, security and privacy of spatio-temporal and trajectory information. Another challenge is finding, combining and creating suitable learning modules to handle the inherent constraints of mobile learning, resource-poor mobile devices and ad-hoc networks. The aim of this research is to design, develop and implement the cutting edge context-aware and ubiquitous self-directed learning methodologies using ad-hoc and sensor networks. The emphasis of our work is on defining an appropriate mobile learning object and the service adaptation descriptions as well as providing mechanisms for ad-hoc service discovery and developing concepts for the seamless integration of the learning objects and their contents with a particular focus on preserving data and privacy. The research involves a combination of modeling, designing, and developing a mobile learning system in the absence of a networking infrastructure that integrates sensory data to support ubiquitous learning. The system includes mechanisms to allow content exchange among the mobile ad-hoc nodes to ensure consistency and availability of information. It also provides an on-the-fly content service discovery, query request, and retrieving data from mobile nodes and sensors.

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. β-adrenergic receptor (β-AR) stimulation induces cardiac myocyte apoptosis in vitro and in vivo. Neurofibromin 2 (NF2) is a member of the ezrin/radixin/moesin (ERM) family of proteins. Post-translational modifications such as phosphorylation and sumoylation affect NF2 activity, subcellular localization and function. Here, we tested the hypothesis that β-AR stimulation induces post-translational modifications of NF2, and NF2 plays a pro-apoptotic role in β-AR-stimulated myocyte apoptosis. Methods and results Treatment of adult rat ventricular myocytes (ARVMs) with β-AR agonist (isoproterenol) for 15 min increased phosphorylation (serine-518) and sumoylation of NF2. Co-immunoprecipi-tation assay confirmed β-AR-stimulated sumoylation of NF2. β-AR stimulation enhanced nuclear translocation of phosphorylated and sumoylated NF2. Specific inhibition of β1-AR and protein kinase A (PKA) decreased β-AR-stimulated increase in NF2 post-translational modifications, while inhibition of β2-AR had no effect. Activation of adenylyl cyclase using forskolin (FSK) mimicked the effects of β-AR stimulation. β-AR stimulation and expression of wild-type (WT)-NF2 using adenoviruses increased phosphorylation of mammalian sterile like kinase-1/2 (MST1/2) and yes activated protein (YAP), downstream targets of NF2. Knockdown of NF2 using siRNA in H9C2 cardiomyocytes decreased β-AR-stimulated increase in NF2 and YAP phosphorylation. siRNA-mediated knockdown of NF2 decreased β-AR-stimulated increase in apoptosis, while expression of WT-NF2 induced apoptosis in ARVMs. Expression of WT-NF2 stimulated the mitochondrial death pathway as evidenced by activation of c-Jun N-terminal Kinases (JNKs), and increase in cytosolic cytochrome c levels and Bax expression. Conclusion β-AR stimulation affects post-translational modifications of NF2 via the involvement β1-AR/PKA/cAMP pathway, and NF2 plays a pro-apoptotic role in β-AR-stimulated myocyte apoptosis via the phosphorylation (inactivation) of YAP and involvement of mitochondrial death pathway.

In the human body, fungi and bacteria share many niches where the close contact of these organisms maintains a balance among the microbial population. However, when this microbial balance is disrupted, as with antibiotic treatment, other bacteria or fungi can grow uninhibited. C. albicans is the most common opportunistic fungal pathogen affecting humans and can uniquely control its morphogenesis between yeast, pseudohyphal, and hyphal forms. Numerous studies have shown that C. albicans interactions with bacteria can impact its ability to undergo morphogenesis; however, the genetics that govern this morphological control via these bacterial interactions are still relatively unknown. To aid in the understanding of the cross-kingdom interactions of C. albicans with bacteria and the impact on morphology we utilized a haploinsufficiency based C. albicans mutant screen to test for the ability of C. albicans to produce hyphae in the presence of three bacterial species (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus). Of the 18,144 mutant strains tested, 295 mutants produced hyphae in the presence of all three bacterial species. The 295 mutants identified 132 points of insertion, which included identified/predicted genes, major repeat sequences, and a number of non-coding/unannotated transcripts. One gene, CDR4, displayed increased expression when co-cultured with S. aureus, but not E. coli or P. aeruginosa. Our data demonstrates the ability to use a large scale library screen to identify genes involved in Candida-bacterial interactions and provides the foundation for comprehending the genetic pathways relating to bacterial control of C. albicans morphogenesis.

In human rehabilitation medicine, dexamethasone-phosphate is theoretically iontophoresed to localized subcutaneous tissue where conversion to dexamethasone occurs. This delivery system has recently been introduced into veterinary medicine for the same purpose. However, the pharmacokinetic justification for parenteral delivery of this prodrug remains undocumented. Utilizing iontophoretic methods that are relevant to both human and veterinary clinical practice, the present investigation compared injection and iontophoresis of dexamethasone-phosphate into the equine tibiotarsal joint, also known as the tarsocrual joint. The tibiotarsal joints of seven horses were injected with 4 mL of 6 mg/mL dexamethasone-phosphate. With a similar drug concentration and over the same application site, six different horses underwent simultaneous cathodic iontophoresis (4 mA, 40 min) or passive application (0 mA, 40 min) on contralateral limbs. Following all applications, tibiotarsal joint synovium was collected. Local venous blood samples were also collected from the iontophoretic and passive application sites for analysis of plasma drug concentrations. Because of the potential for conversion of dexamethasone-phosphate to dexamethasone, an extraction and analysis protocol was developed for both chemicals. The technique demonstrated a linear range of detection (0.39-12 μg/mL) and a capability for measuring both chemicals in plasma and synovium. Conversion of dexamethasone-phosphate to dexamethasone occurred during synovial incubation (37 °C) and following freeze-thaw cycles. In contrast to the measurable synovial concentrations of dexamethasone-phosphate (2.3±0.96 mg/mL) and dexamethasone (0.27±0.07 mg/mL) following injection, neither drug was detected in the synovium or the local venous blood following iontophoretic or passive applications. In conclusion, these results do not confirm iontophoretic or passive delivery of measurable dexamethasone-phosphate into the tibiotarsal joint using current clinical methods.

In the human body, fungi and bacteria share many niches where the close contact of these organisms maintains a balance among the microbial population. However, when this microbial balance is disrupted, as with antibiotic treatment, other bacteria or fungi can grow uninhibited. C. albicans is the most common opportunistic fungal pathogen affecting humans and can uniquely control its morphogenesis between yeast, pseudohyphal, and hyphal forms. Numerous studies have shown that C. albicans interactions with bacteria can impact its ability to undergo morphogenesis; however, the genetics that govern this morphological control via these bacterial interactions are still relatively unknown. To aid in the understanding of the cross-kingdom interactions of C. albicans with bacteria and the impact on morphology we utilized a haploinsufficiency based C. albicans mutant screen to test for the ability of C. albicans to produce hyphae in the presence of three bacterial species (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus). Of the 18,144 mutant strains tested, 295 mutants produced hyphae in the presence of all three bacterial species. The 295 mutants identified 132 points of insertion, which included identified/predicted genes, major repeat sequences, and a number of non-coding/unannotated transcripts. One gene, CDR4, displayed increased expression when co-cultured with S. aureus, but not E. coli or P. aeruginosa. Our data demonstrates the ability to use a large scale library screen to identify genes involved in Candida-bacterial interactions and provides the foundation for comprehending the genetic pathways relating to bacterial control of C. albicans morphogenesis.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assembled into two categories; cyclooxygenase (COX-1) sparing inhibitors of COX-2 and non-selective NSAIDs. Diclofenac (DICLO) is a non-selective NSAID that has been linked to serious side effects including gastric ulcers and renal injury. In this study, we examine the effect of poly(lactic-co-glycolic) acid nanoformulation on DICLO-associated adverse events and pharmacokinetics using a nanoparticle (NP) formulation previously developed in our laboratory.MATERIALS AND METHODS: Rats were administered a single dose of methylcellulose (VEH), blank NP, DICLO (10 mg/kg), or a DICLO-NP suspension equivalent to the DICLO dose. Urinary and blood parameters were measured at baseline and following treatment. Duodenal and gastric prostaglandin E2 (PGE2) and duodenal myeloperoxidase (MPO) were collected to assess inflammation at 24 hrs post-treatment.RESULTS: The mean percent change from baseline in sodium excretion rate (µmol/min/100 g body weight) differed significantly from VEH in the NP (p < 0.0001), DICLO (p < 0.0001), and DICLO-NP (p = 0.0001) groups. The differences among groups did not reach significance for plasma sodium or potassium concentrations, potassium excretion rate, gastric PGE2, or intestinal biomarker concentrations. Regarding renal histopathology, DICLO produced considerably more necrosis compared to VEH; while DICLO-NP did not elicit notable differences from VEH.CONCLUSIONS: Our results suggest that over the duration and dosage examined, DICLO-NP may reduce renal necrosis without influencing other side effects or drug characteristics.

C-reactive protein (CRP) is a cyclic pentameric protein whose major binding specificity, at physiological pH, is for substances bearing exposed phosphocholine moieties. Another pentameric form of CRP, which exists at acidic pH, displays binding activity for oxidized LDL (ox-LDL). The ox-LDL-binding site in CRP, which is hidden at physiological pH, is exposed by acidic pH-induced structural changes in pentameric CRP. The aim of this study was to expose the hidden ox-LDL-binding site of CRP by site-directed mutagenesis and to generate a CRP mutant that can bind to ox-LDL without the requirement of acidic pH. Mutation of Glu 42, an amino acid that participates in intersubunit interactions in the CRP pentamer and is buried, to Gln resulted in a CRP mutant (E42Q) that showed significant binding activity for ox-LDL at physiological pH. For maximal binding to ox-LDL, E42Q CRP required a pH much less acidic than that required by wild-type CRP. At any given pH, E42Q CRP was more efficient than wild-type CRP in binding to ox-LDL. Like wild-type CRP, E42Q CRP remained pentameric at acidic pH. Also, E42Q CRP was more efficient than wild-type CRP in binding to several other deposited, conformationally altered proteins. The E42Q CRP mutant provides a tool to investigate the functions of CRP in defined animal models of inflammatory diseases including atherosclerosis because wild-type CRP requires acidic pH to bind to deposited, conformationally altered proteins, including ox-LDL, and available animal models may not have sufficient acidosis or other possible modifiers of the pentameric structure of CRP at the sites of inflammation.